BIAL and moksha8 announce exclusive license for the commercialization of eslicarbazepine acetate (Zebinix® / Exalief®) in Brazil and Mexico

BIAL and moksha8 announce exclusive license for the commercialization of eslicarbazepine acetate (Zebinix® / Exalief®) in Brazil and Mexico

Wayne, PA, USA, Porto, Portugal. July 15, 2014 – BIAL a research based international pharmaceutical company and moksha8 a leading specialty pharmaceutical company in Latin America announced today an exclusive license for the commercialization of eslicarbazepine acetate (Zebinix® / (Exalief®) in Brazil and Mexico for the treatment of epilepsy.

Epilepsy is one of the most common neurological diseases, affecting 70 million worldwide and up to 5 million people in Latin America – and the successful treatment of partial-onset seizures (the most common type of epilepsy) remains a challenge. Up to 40% of patients with partial seizures do not achieve sustained seizure control with current treatments (1). There are many patients with epilepsy whose condition is difficult to treat with existing anti-epileptic drugs. Eslicarbazepine acetate ® is an add-on (adjunctive) therapy for adults with partial-onset seizures, with or without secondary generalization (where the seizure spreads to both sides of the brain).

"moksha8 is committed to providing the highest quality products to physicians and patients to improve the treatment of critical CNS indications," said Simba Gill, CEO of moksha8. "Epilepsy is a serious condition that not only affects the people who suffer from seizures, but also their family, caregivers and friends. We look forward to bringing eslicarbazepine acetate to Brazil and Mexico."

"Eslicarbazepine acetate developed by BIAL is the outcome of BIAL's longstanding scientific commitment to CNS research and development and the desire to improve the quality of life in those patients with poor seizure control," commented Antonio Portela, CEO of BIAL. "We are pleased to be working with moksha8 in Brazil and Mexico as a high quality partner in two of the largest markets in Latin America."

The Latin America retail pharmaceutical market is estimated by IMS at USD $68 billion in 2013, growing at 12% CAGR to over USD $110 billion by 2017. Brazil is expected to be the fourth largest pharmaceutical market in the world by 2017.

Eslicarbazepine acetate was approved by the European Commission in 2009 based on data showing that it reduces seizure frequency and improves health-related quality of life and is commercialized in the European Union under the trade name Zebinix®. Eslicarbazepine acetate was approved by the U.S., Food and Drug Administration (FDA), in November 2013 and is sold in the U.S. under the trade name APTIOM®. Eslicarbazepine acetate does not yet have a marketing authorization in Brazil or Mexico.

About epilepsy, partial-onset seizures and their treatment
Epilepsy is a chronic neurological disease characterized by abnormal discharges of neuronal activity causing seizures. Clinically, these manifest as convulsions or jerking of muscles. Depending on the seizure type, seizures may be limited to one part of the body, or may be generalized to involve the whole body. Patients may also experience abnormal sensations, altered behaviour or altered consciousness. Epilepsy is a disorder with many possible causes. Often the cause of epilepsy is unknown. However, anything that disturbs the normal pattern of neuron activity - from illness to brain damage to abnormal brain development, can lead to seizures.

Epilepsy is characterised by abnormal firing of impulses from nerve cells in the brain. In partial-onset seizures, these bursts of electrical activity are initially focused in specific areas of the brain, but may become more generalised; the symptoms vary according to the affected areas. Nerve impulses are triggered via voltage-gated sodium channels in the nerve cell membrane.
Treatment of partial-onset seizures, the most common type of epilepsy, presents a constant challenge – up to 40% of patients with partial-onset seizures do not achieve sustained seizure control with current anti-epileptic drugs(1). Furthermore, central nervous system related adverse events, such as lightheadedness (dizziness), somnolence (sleepiness), and cognitive slowing (attention and memory deficits), are highly prevalent with existing anti-epileptic agents. Hence, there is a need for new anti-epileptic agents that offer effective reduction in seizure frequency combined with a favourable safety profile.

About eslicarbazepine acetate (Zebinix® / Exalief®)
Eslicarbazepine acetate is a once-daily, voltage-gated sodium channel blocker. It preferentially targets the inactivated state of the ion channel, preventing its return to the active state, and thereby reduces repetitive neuronal firing (2-4).

Clinical data
The EU approved file is based on efficacy and safety data from an initial proof-of concept phase II study (5) and four subsequent phase III randomized, placebo controlled studies in more than 1700 patients with refractory partial-onset seizures (6-11). These patients had a history of at least four partial-onset seizures per month despite treatment with up to three concomitant anti-epileptic drugs (6-11).

Efficacy
Over the 12-week maintenance period, eslicarbazepine acetate 800mg and 1200mg once-daily significantly reduced seizure frequency, and was significantly more effective than placebo (6-11). Long-term safety and maintenance of therapeutic effect was demonstrated in one-year open-label extensions of these studies (12, 13).

Tolerability
In the Phase III clinical trials adverse events mainly occurred during the first 6 weeks of treatment and the majority of patients experienced adverse events of mild to moderate intensity (6-11). After 6 weeks of treatment, there were no observed differences in the incidence of side effects between patients treated with eslicarbazepine acetate and the placebo group. Treatment-emergent adverse events affecting >10% of patients in the pivotal studies were dizziness and somnolence (2, 6-11).

Quality of life and depressive symptoms
The effect of slicarbazepine acetate on quality of life was assessed using the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) scale. There was a statistically and clinically significant improvement from baseline during long-term open-label therapy, including a mean relative improvement in overall quality of life and improvements in individual elements of the QOLIE-31 scale including seizure worry, emotional wellbeing, energy/fatigue, medication effects and social function (12, 13). Improvement in depressive symptoms was also measured using the Montgomery-Asberg Depression Rating Scale (MADRS). During long-term, open-label therapy, eslicarbazepine acetatedemonstrated a statistically significant improvement from baseline in the overall MADRS score and individual domains of the MADRS scale including pessimistic thoughts, concentration difficulties, apparent sadness and inner tension (12, 13).

About BIAL Group
BIAL is a research based, privately owned, international pharmaceutical group with products available in more than 50 countries. Strongly committed to therapeutic innovation, BIAL´s research and development (R&D) is focused on the central nervous system, cardiovascular system and allergic immunotherapy, and currently has several innovative programs under development, which it expects to bring to the market within the next years. The R&D projects of the company are also focused on the ongoing clinical development program of eslicarbazepine acetate, which is already commercialised in the United States and in several European markets. This program comprises studies designed to evaluate new therapeutic indications, such as adjuvant treatment in children and monotherapy.

For additional information on BIAL, please visit the company's web site at: www.bial.com

About moksha8
moksha8 is a leading Latin American pharmaceutical company, with a core focus on commercializing the highest quality medicines with best in class operations and strong FCPA compliance. The company launched its commercial operations in 2008 in Brazil and Mexico promoting primarily CNS products. moksha8 has strategic alliances with Forest Laboratories, GSK, Sandoz, Bial, Aurobindo and Accord. The company was founded by Simba Gill and TPG Biotechnology. Major investors include TPG Biotechnology and Montreux Equity Partners. For additional information on moksha8, please visit the company's web site at www.moksha8.com.